Application of Covalent Binding Body Burden in the HµREL Human Hepatocyte Coculture Model for Reactivity Risk Assessment of Metabolically Low Turnover Drugs.

The human hepatocyte suspension model has been a valuable tool to study covalent binding (CVB) for compounds that form reactive metabolites. However, accurately measuring CVB values with the suspension model becomes challenging for metabolically low turnover compounds. In this study, we evaluated the HµREL human hepatocyte coculture model relative to existing literature using human hepatocyte suspension for drugs of known drug-induced liver injury category. Our results indicate that this coculture model provides ample metabolic turnover to reproducibly measure CVB. It is sufficiently robust to apply a predefined 1 mg/day CVB body burden threshold for risk assessment to guide our discovery programs, allowing for expanded coverage to include metabolically low turnover compounds.

Aquatic macroinvertebrate community responses to pollution of perfluoroalkyl substances (PFAS): Can we define threshold body burdens?

The pollution of per- and polyfluorinated alkyl substances (PFAS) in aquatic environments is a worldwide concern of which the ecological impact is still not well understood. Especially field-based effect studies in aquatic ecosystems are generally lacking, creating a knowledge gap that goes along with monitoring and regulatory challenges. Therefore, this study examined if bioaccumulated PFAS concentrations could be related to ecological responses assessed by changes in the macroinvertebrate community structure. In addition, threshold body burdens that are protective of ecological damage were estimated. Aquatic macroinvertebrates were sampled in 30 streams across Flanders (Belgium) and 28 PFAS target analytes were measured in three resident taxa (Gammarus sp., Asellus sp. and Chironomus sp.) and translocated zebra mussels (Dreissena polymorpha). The macroinvertebrate community structure was assessed by calculating the Multimetric Macroinvertebrate Index Flanders (MMIF). Primarily long-chain perfluorinated carboxylic acids (PFCAs) were detected in both resident taxa (passive biomonitoring) and zebra mussels (active biomonitoring). Based on a 90th quantile regression model, safe threshold body burdens could be calculated for PFTeDA (7.1 ng/g ww) and ΣPFAS (2264 ng/g ww) in Gammarus sp. and for PFOA (5.5 ng/g ww), PFDoDA (1.7 ng/g ww), PFTrDA (0.51 ng/g ww), PFTeDA (2.4 ng/g ww), PFOS (644 ng/g ww) and ΣPFAS (133 ng/g ww) in zebra mussel. An additional threshold value was calculated for most compounds and species using the 95th percentile method. However, although these estimated thresholds are pertinent and indicative, regulatory applicability requires further lines of evidence and validation. Nevertheless, this study offers first-time evidence of associations between accumulated PFAS concentrations in invertebrates and a reduced ecological water quality in terms of macroinvertebrate community structure and highlights the potential of Gammarus sp. and zebra mussels to serve as reliable PFAS biomonitoring species.

Association of size, climatic factors, and mercury body burdens with movement behavior in American alligators.

Animal movement behavior provides insight into organismal and ecological function. These functions are often disturbed by anthropogenic influences, such as urbanization and habitat fragmentation, yet the effects of long-term exposures to environmental contaminants on movement have yet to be examined. The long lifespans and broad diets of crocodilians often lead to bioaccumulation of persistent contaminants and confer a marked vulnerability to consequent physiological effects. In this study, we investigate the relationships between blood concentrations of mercury (Hg), a widespread contaminant with well characterized neurotoxicity, and movement patterns in free living, naturally exposed American alligators (Alligator mississippiensis). We sampled adult male alligators from two former nuclear cooling reservoirs with different Hg contamination histories and placed GPS transmitters on a subset of individuals from each reservoir (13 total). Data collected over the ensuing two years were analyzed using a linear mixed effects framework combined with AICc model selection to resolve the relationships linking seasonal alligator movement (daily activity (s) and daily distance (m)) and home range to climate conditions, individual traits, and blood Hg concentrations (mg/kg; wet weight). We found that climate conditions, alligator size (snout-vent-length), and blood Hg concentrations all influence alligator daily activity but do not contribute to alligator daily movement (distance). Furthermore, we found that blood Hg concentrations were strongly correlated with seasonal home range size where individuals with elevated Hg had larger home ranges in spring, fall, and winter. These findings provide insight into how climate, anthropogenic contaminants, and individual traits relate to alligator movement patterns across seasons.

Mechanistic modelling of amphibian body burdens after dermal uptake of pesticides from soil.

Amphibians are currently considered to be covered by pesticide Environmental Risk Assessment schemes by surrogacy assumptions of exposure and susceptibility based on typical laboratory test species such as fish, mammals, and birds. While multiple reviews have shown for this approach to be adequate in the case of aquatic stages, the same cannot be definitively stated for terrestrial stages. Concerns have risen that exposure of amphibians is likely to be highly influenced by dermal absorption, primarily due to the high permeability of their skin and the lack of a protective layer, such as fur or feathers. It is thus hypothesized that dermal uptake could be a significant route of exposure. Consequently, it is necessary to determine the relative importance of different exposure routes that might affect the integrated toxicity outcome for terrestrial amphibian life-stages. Here, a one-compartment Toxicokinetic model was derived and tested using a publicly available dataset containing relevant exposure and uptake information for juvenile anurans exposed to 13 different pesticides. Modelled body burdens were then compared to measured burdens for a total of 815 individuals. Overall, a good concordance between modelled and measured values was observed, with the predicted and measured body burdens differing by a factor of 2 on average (overall R2 of 0.80 and correlation coefficient of 0.89), suggesting good predictivity of the model. Accordingly, the model predicts realistic body burdens for a variety of frog and toad species, and overall, for anurans. As the model includes rehydration (implicit in the evaluated studies) but currently does not account for metabolism, it can be seen as a worst-case assessment. We suggest toxicokinetic models, such as the one here presented, could be used to characterize dermal exposure in amphibians, screen for pesticides of concern, and prioritize risk assessment efforts, whilst reducing the need for de novo vertebrate testing.

Total body burden of neurotoxicant Hg in Chinese mitten crab (Eriocheir sinensis) - Considerations of distribution and human risk assessment.

The Chinese mitten crab (Eriocheir sinensis) is considered one of the 100 most invasive alien species in the world. Despite this, its role in ecosystems, among others, in the trophodynamics of pollutants including mercury, is still not fully understood. Becoming an increasingly important and widespread element of the trophic chain in new areas arouses interest from humans as consumers. Hence it is important to determine the level of contaminants (including Hg) in alien species. In the present study, great attention was paid separately to the soft tissues and hard tissues of the exoskeleton, which may play an important role in the detoxification of the crab's body from toxic Hg. The study was conducted on crabs collected in 2011-2021 in the Vistula Lagoon. Concentrations of total mercury and its forms were carried out using a Direct Mercury Analyzer, DMA-80 (Milestone, Italy). The present study showed that mercury accumulation of the crab's body largely occurred through the gills, followed by the oral route. The distribution of Hg in the crab's organs was related to the trophic origin of the mercury, while halide-bound mercury and semilabile forms from the respiration (filtration) process were redistributed into the crab's exoskeleton. Male crabs, compared to females, had a higher Hg burden on internal organs such as their hepatopancreas and gonads. Hg concentration in hard tissues was closely related to the type of mineralization of the carapace. The elimination of Hg from the muscles and from the hepatopancreas into the carapace was one of the important detoxification processes of the crab's body. Thus, moulting crabs effectively remove Hg protecting its body from the neurotoxin. As a result, a smaller Hg load is biomagnified, making the crab's muscle tissue fit for human consumption. The observed decrease in Hg concentrations from 2011 to 2021, as well as the spatial variability of Hg in the crab's muscles, testify that the crab can serve as a biomonitor for ecosystem changes.

Chemical contaminants in blood and their implications in chronic diseases.

Artificial chemical products are widely used and ubiquitous worldwide and pose a threat to the environment and human health. Accumulating epidemiological and toxicological evidence has elucidated the contributions of environmental chemical contaminants to the incidence and development of chronic diseases that have a negative impact on quality of life or may be life-threatening. However, the pathways of exposure to these chemicals and their involvements in chronic diseases remain unclear. We comprehensively reviewed the research progress on the exposure risks of humans to environmental contaminants, their body burden as indicated by blood monitoring, and the correlation of blood chemical contaminants with chronic diseases. After entering the human body through various routes of exposure, environmental contaminants are transported to target organs through blood circulation. The application of the modern analytical techniques based on human plasma or serum specimens is promising for determining the body burden of environmental contaminants, including legacy persistent organic pollutants, emerging pollutants, and inorganic elements. Furthermore, their body burden, as indicated by blood monitoring correlates with the incidence and development of metabolic syndromes, cancers, chronic nervous system diseases, cardiovascular diseases, and reproductive disorders. On this basis, we highlight the urgent need for further research on environmental pollution causing health problems in humans.

ON THE METHODOLOGY OF PASSPORT DOSES CALCULATION FOR UKRAINIAN SETTLEMENTS RADIOACTIVELY CONTAMINATED DUE TO THE CHORNOBYL NPP ACCIDENT. / ЩОДО МЕТОДИКИ РОЗРАХУНКУ ПАСПОРТНИХ ДОЗ НАСЕЛЕНИХ ПУНКТІВ УКРАЇНИ, ЯКІ ЗАЗНАЛИ РАДІОАКТИВНОГО ЗАБРУДНЕННЯ В РЕЗУЛЬТАТІ АВАРІЇ НА ЧАЕС.

OBJECTIVE: scientific substantiation of the new methodology for estimation of passport doses of the settlementswhich belong to Zone of Unconditional (obligatory) Resettlement, or 2nd zone and Zone of Granted VoluntaryResettlement, or 3rd zone in the framework of dosimetric passportization in accordance with the legislation ofUkraine. MATERIALS AND METHODS: 37 years after the accident, radioactive contamination of the environment has significantly decreased. However, it is still necessary to carry out ecological and dosimetric monitoring and apply countermeasures in certain territories of Ukraine affected by the accident at the Chornobyl Nuclear Power Plant: restriction of the consumption of locally produced milk, forest products, etc. The methodology, which was since 1996 used to estimate the passport doses of Ukrainian settlements, no longer corresponds to the current level of scientific knowledge about radioactive contamination of environment. The new methods of passport doses calculating presented in the work involves the use of a model whose parameters are determined by the types, quality and completeness of radio-ecological and dosimetric monitoring carried out on the radioactively contaminated territories in 1986-2013. The methodology takes into account the specific of radioactive contamination of each settlement. The passport dose of external exposure is reconstructed only from 137Cs radionuclide, because the contributions of other Chornobyl radionuclides influence the radiation dose only in the first years after the accident. The passport dose of internal exposure is formed as a result of the consumption of 137Cs contaminated food products. It is calculated depending on the availability in the settlement in the current year of the results of measurements of the 137Cs radionuclide activity incorporated in the human body using a whole body counter (WBC) and the activity of 137Cs in the private milk. At the same time, priority is given precisely to the results of WBC measurements of 137Cs. RESULTS AND CONCLUSIONS: A new methodology (Methodology-2023) for passport doses calculation of Ukrainian settlements was substantiated. A comparison of passport doses based on the results of radioecological and dosimetric monitoring in 2011 calculated by Methodology-2023 and passport doses calculated by Methodology-96 was made.Passport doses calculated by Methodology-2023 increased by 40 % on average compared to doses calculated by Methodology-96. At the same time, passport doses of internal radiation calculated by the new methodologyincreased by 1.5 times, and passport doses of external radiation increased by 1.7 times. The passport dose of 2011, calculated by Methodology-2023, exceeds the legally established limit of 1 mSv in 71 settlements, most of which are located in Korostenkyi raion of Zhytomyr Oblast.

Dynamic exposure and body burden models for per- and polyfluoroalkyl substances (PFAS) enable management of food safety risks in cattle.

With increasing global focus on planetary boundaries, food safety and quality, the presence of per- and polyfluoroalkyl substances (PFAS) in the food chain presents a challenge for the sustainable production and supply of quality assured food. Consumption of food is the primary PFAS exposure route for the general population. At contaminated sites, PFAS have been reported in a range of agricultural commodities including cattle. Consumer exposure assessments are complicated by the lack of validated modelling approaches to estimate PFAS bioaccumulation in cattle. Previous studies have shown that PFAS bioaccumulation in livestock is influenced by environmental, spatial and temporal factors that necessitate a dynamic modelling approach. This work presents an integrated exposure and population toxicokinetic (PopTK) model for cattle that estimates serum and tissue concentrations of PFAS over time. Daily exposures were estimated from intakes of water, pasture, and soil, and considered animal growth, seasonal variability (pasture moisture content and temperature) and variable PFAS concentrations across paddocks. Modelled serum and tissue estimates were validated against monitoring data from Australian and Swedish cattle farms. The models were also used to develop and test practical management options for reducing PFAS exposure and to prioritise remediation for farms. Model outputs for exposure management scenarios (testing cattle rotation and targeted supplementation of feed and water) showed potential for marked reductions in consumer exposures from cattle produce.

Polychlorinated biphenyl (PCB) half-lives in humans: A systematic review.

This manuscript presents a systematic review of PCB half-lives reported in the scientific literature. The review was completed in accordance with PRISMA guidelines and included a review of almost 1000 peer-reviewed publications. In total, 26 articles were found to report half-lives in humans, with the majority of data coming from studies performed in North America on individuals suspected to have been exposed to PCBs. Terminology for reporting PCB half-lives was inconsistent, so we have attempted to consolidate this and recommend using either "apparent half-life" or "intrinsic half-life" in future studies. Within the literature, values for reported half-lives varied considerably for different PCBs. Less chlorinated PCBs generally have shorter half-lives than more chlorinated PCBs. It was interesting to note the large variability of half-lives reported for the same PCB. For example, the reported half-life for PCB 180 varied by nearly 3 orders of magnitude (0.34 years-300 years). Our review identified that the half-lives estimated were largely dependent on the studied cohort. We discuss the importance of PCB body burden, degree of chlorination and PCB structure, gender, age, breastfeeding, BMI, and smoking status on half-life estimations. We also identified significantly shorter half-lives for some PCBs in occupationally exposed individuals compared to results reported from the general population. PCB half-lives are not the same for every PCB or every individual. Therefore, careful consideration is needed when these values are used in human exposure studies.

Cadmium body burden and health effects after restoration of cadmium-polluted soils in cadmium-polluted areas in the Jinzu River basin.

BACKGROUND: Itai-itai disease is caused by environmental cadmium (Cd) pollution in the Jinzu River basin in Japan. To reduce the Cd contamination of rice, soil restoration of paddy fields was carried out. We evaluated the effect of soil restoration on the health status of residents of the former Cd-polluted area. METHODS: Participants were 1,030 men and 944 women who lived in the area of restoration of Cd-polluted rice paddies. First morning urine was collected and urinary Cd, ß2-microglobulin (ß2MG), and N-acetyl-ß-D-glucosaminidase (NAG) levels were measured. Associations among age, years of residence before and after soil restoration, and urinary Cd, ß2MG, and NAG levels were evaluated by multiple regression analysis. RESULTS: The geometric mean (interquartile range) of urinary Cd (µg/g Cr) was 1.00 (0.58-1.68) in men and 1.67 (1.02-2.91) in women. The geometric means of urinary ß2MG (µg/g Cr) and NAG (U/g Cr) were 174.6 (92.6-234.2) and 1.47 (0.72-3.14) in men, and 217.6 (115.3-28.7) and 1.48 (0.73-2.96) in women, respectively. Urinary Cd, ß2MG, and NAG were significantly positively correlated (p < 0.01 all). Age and duration of residence in the Cd-polluted area before soil restoration were independently associated with urinary Cd, ß2MG, and NAG. Among the 916 participants who had resided in the area before the soil restoration, urinary Cd concentrations were significantly higher, thus by 1.03-fold (95% CI, 1.01-1.04) in men and 1.03-fold (95% CI, 1.01-1.05) in women, when the years of residence before soil restoration by each 5-years increment. By contrast, urinary Cd concentrations were significantly lower, thus 0.97-fold (95% CI, 0.96-0.99) lower in men and 0.97-fold (95% CI, 0.95-0.99) lower in women, by each 5-year increment of residence after soil restoration. A similar association was observed for urinary ß2MG concentration, and no significant association was observed for urinary NAG levels in men or women. CONCLUSIONS: Cd exposure and associated renal tubular dysfunction in residents of a former Cd-polluted area were influenced by Cd exposure from the environment prior to soil restoration. Soil restoration in Cd-polluted areas reduced the Cd exposure of local residents.

Can oestrogenic activity in air contribute to the overall body burden of endocrine disruptors?

Endocrine disruptors (EDCs) are emerging contaminants that are harmful to health. Human exposure occurs mainly through ingestion or dermal contact, but inhalation could be an additional exposure route; therefore, this study was conducted to evaluate the oestrogenic activity of airborne particulate matter (PM). Outdoor PM was collected for a year in five Italian sites and extracted with organic solvents (four seasonal extracts/site). The oestrogenic activity was assessed using a gene reporter assay (MELN), and the risk to human health through inhalation was quantified using the results. Moreover, extracts were analysed to assess cytotoxicity (WST-1 and LDH assays) on human bronchial cells (BEAS-2B). The extracts induced a significant cytotoxicity and oestrogenic activity. Oestrogenic activity showed a seasonal trend and was correlated with concentrations of benzo(a)pyrene and toxic equivalency factor. Although a low inhalation cancer risk was found, this study confirmed that oestrogenic activity in air could contribute to overall health risks due to EDC exposure.

Integral Study of Paramecium caudatum Acute and Chronic Toxicity, Sites of Entry and Distribution, Bioconcentration and Body Burdens of Five Metals.

An integral analysis of the acute and chronic toxicity, bioaccumulation, sites of entry, and distribution of four trace metals: copper, iron, lead, and nickel, and the non-trace metal mercury were performed in the ciliate Paramecium caudatum. Mercury was the fastest metal accumulated, and the most toxic. The sensitivity of Paramecium caudatum to the five metals tested (Cu, Fe, Hg, Ni, and Zn) falls in the range of other ciliate species. We observed similarities between the toxicity of the five metals to the ciliate P. caudatum with the rotifer Euchlanis dilatata: (a) Mercury was the most toxic metal in terms of acute and body burdens. (b) Acute values were very similar in both species, Hg as the most toxic and Fe as the less toxic, (c) the vacuole/ingestion chronic tests were more sensitive than growth inhibition chronic tests. These analyses would ideally help generate safer guidelines for protecting aquatic biota.

Environmental organic contaminant body burdens and GC-MS based untargeted metabolomics in mediterranean mussels from Port Phillip Bay, Australia☆.

Mussels were collected from four coastal sites around Port Phillip Bay, Australia in Mar and Apr 2021). Body burdens of Polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and organochlorine pesticides (OCPs) were measured and the possible sources of toxicants discussed. In addition, a gas chromatography-mass spectrometry (GC-MS) based untargeted metabolomics analysis was performed using the mantle tissues of mussels. Correlations between the results of contaminant body burdens and metabolic variations were investigated. The results demonstrated that high accumulations of low-molecular-weight PAHs were found in mussels. High body burdens of PCBs and OCPs were only found at mussels from the site close to the river mouth. Some of the metabolic pathways were correlated with the accumulation of PAHs. No correlations were found between PCB and OCP accumulations and metabolic abundances. According to the food and environmental standards of the European Union (EU), the PAH, PCB, and OCP accumulation in mussels in this study are a serious food safety concern.

Radioactive contamination in feral dogs in the Chernobyl exclusion zone: Population body-burden survey and implications for human radiation exposure.

This report describes a two-year effort to survey the internal 137Cs and external ß-emitter contamination present in the feral dog population near the Chernobyl nuclear power plant (ChNPP) site, and to understand the potential for human radiation exposure from this contamination. This work was performed as an integral part of the radiation safety and control procedures of an animal welfare oriented trap-neuter-release (TNR) program. The measurement program focused on external contamination surveys using handheld ß-sensitive probes, and internal contamination studies using a simple whole-body counter. Internal 137Cs burden was measured non-invasively during post-surgical observation and recovery. External ß contamination surveys performed during intake showed that 21/288 animals had significant, removable external contamination, though not enough to pose a large hazard for incidental contact. Measurements with the whole-body counter indicated internal 137Cs body burdens ranging from undetectable (minimum detection level ∼100 Bq/kg in 2017, ∼30 Bq/kg in 2018) to approximately 30,000 Bq/kg. A total of 33 animals had 137Cs body-burdens above 1 kBq/kg, though none posed an external exposure hazard. The large variation in the 137Cs concentration in these animals is not well-understood, could be due to prey selection, access to human food scraps, or extended residence in highly contaminated areas. The small minority of animals with external contamination may pose a contamination risk allowing exposures in excess of regulatory standards.

An impact-based environmental risk assessment model toolbox for offshore produced water discharges.

We present a novel approach to environmental risk assessment of produced water discharges based on explicit impact and probability, using a combination of transport, fate and toxicokinetic-toxicodynamic models within a super-individual framework, with a probabilistic element obtained from ensemble simulations. Our approach is motivated by a need for location and species specific tools which also accounts for the dynamic nature of exposure and uptake of produced water components in the sea. Our approach is based on the well-established fate model DREAM, and accounts for time-variable exposure, considers body burden and effects for specific species and stressors, and assesses the probability of impact. Using a produced water discharge in the Barents Sea, with early life stages of spawning haddock, we demonstrate that it is possible to conduct a model-based risk assessment that highlights the effect of natural variations in environmental conditions. The benefits, limitations and potential for further improvements are discussed.

Cumulative Exposure to Phthalates and Their Alternatives and Associated Female Reproductive Health: Body Burdens, Adverse Outcomes, and Underlying Mechanisms.

The global birth rate has recently shown a decreasing trend, and exposure to environmental pollutants has been identified as a potential factor affecting female reproductive health. Phthalates have been widely used as plasticizers in plastic containers, children's toys, and medical devices, and their ubiquitous presence and endocrine-disrupting potential have already raised particular concerns. Phthalate exposure has been linked to various adverse health outcomes, including reproductive diseases. Given that many phthalates are gradually being banned, a growing number of phthalate alternatives are becoming popular, such as di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH), di(2-ethylhexyl) adipate (DEHA), and di(2-ethylhexyl) terephthalate (DEHTP), and they are beginning to have a wide range of environmental effects. Studies have shown that many phthalate alternatives may disrupt female reproductive function by altering the estrous cycle, causing ovarian follicular atresia, and prolonging the gestational cycle, which raises growing concerns about their potential health risks. Herein, we summarize the effects of phthalates and their common alternatives in different female models, the exposure levels that influence the reproductive system, and the effects on female reproductive impairment, adverse pregnancy outcomes, and offspring development. Additionally, we scrutinize the effects of phthalates and their alternatives on hormone signaling, oxidative stress, and intracellular signaling to explore the underlying mechanisms of action on female reproductive health, because these chemicals may affect reproductive tissues directly or indirectly through endocrine disruption. Given the declining global trends of female reproductive capacity and the potential ability of phthalates and their alternatives to negatively impact female reproductive health, a more comprehensive study is needed to understand their effects on the human body and their underlying mechanisms. These findings may have an important role in improving female reproductive health and in turn decreasing the number of complications during pregnancy.

Associations of micronutrients exposure with cadmium body burden among population: A systematic review.

BACKGROUND: The absorption and accumulation of cadmium (Cd) within the human body can be influenced by the status of certain micronutrients, while available evidence for the association between micronutrient exposure and Cd body burden remains fragmented and inconsistent. To address this issue, this article reviews and synthesizes epidemiological studies that examine the association between micronutrient exposure and Cd burden in humans, to elucidate the potential association between micronutrient exposure and Cd body burden. METHODS: We conducted a systematic review of epidemiologic studies reporting the association between micronutrient status and Cd body burden among the population. Relevant articles were selected based on predetermined criteria from PubMed, Web of Science, and Scopus databases published from 2000 to 2021. The exposures that were evaluated included micronutrients (zinc, selenium, iron, calcium, and vitamins) status or intakes of them. The outcome of interest was the Cd body burden as indicated by blood Cd or urinary Cd levels. The quality of included studies was assessed using The Joanna Briggs Institute critical appraisal tool. We extracted data from each article, including study design, study site, study population, micronutrient status, Cd body burden, and the correlations between micronutrient status and Cd body burden. RESULTS: Our systematic search yielded 1660 articles. Of these, forty-four were selected for inclusion based on prespecified criteria. These selected articles evaluated the relationship between Cd body burden and seven different micronutrients, namely, selenium (Se), zinc (Zn), calcium (Ca), iron (Fe), vitamin A, vitamin B12, and vitamin D. The majority of studies (n = 41) were observational, while only three were randomized controlled trials. Among the seventeen studies assessing Zn status, ten reported a negative association between serum Zn levels or intake and urinary and blood Cd levels. Results were inconsistent among the ten studies examining the association between Se levels and Cd body burden. Six studies showed that Cd in blood and urine was negatively correlated with serum ferritin (SF), a biomarker of body Fe status. Two studies reported a negative correlation between Ca and blood Cd. CONCLUSIONS: This synthesis of available evidence suggests that certain micronutrients, especially Zn and Fe, may play a role in reducing the Cd body burden among populations. The evidence strongly supports a negative association between Zn, Fe, and Cd body burden, whereas evidence for Se, Ca and vitamins is insufficient to draw definitive conclusions regarding their relationship with Cd body burden. In addition, observational studies limit the ability to infer a causal relationship between micronutrients and Cd body burden, highlighting the need for additional intervention studies. Our review may inform nutrient supplementation guidance, control of Cd body burden, and future research to mitigate the adverse health effects of Cd in the context of global Cd pollution.

Relationship closeness of tolerance to two neonicotinoids with their internal body burden in two estuarine resident marine crustaceans.

The estuarine resident crustacean sand shrimp, Crangon uritai, has a higher tolerance to neonicotinoid insecticides than that of the kuruma prawns, Penaeus japonicus. However, the reason for the differential sensitivities between the two marine crustaceans remains to be understood. This study explored the mechanism underlying differential sensitivities based on insecticide body residues after exposing both said crustaceans to two insecticides (acetamiprid and clothianidin) with or without oxygenase inhibitor piperonyl butoxide (PBO) for 96 h. Two graded-concentration groups were formed; group H (1/15-1 times the 96-h LC50 values) and L (one-tenth the concentration of group H). Results showed that the internal concentration in survived specimens tended to be lower in sand shrimp than in kuruma prawns. Co-treatment of PBO with two neonicotinoids not only increased sand shrimp mortality in the H group, but also altered metabolism of acetamiprid into its metabolite, N-desmethyl acetamiprid. Furthermore, molting during the exposure period enhanced bioconcentration of insecticides, but not affects survival. Collectively, the higher tolerance of sand shrimp than that of kuruma prawns to the two neonicotinoids can be explained by lower bioconcentration potential and more involvement of oxygenase in their alleviating lethal toxicity.

Emerging and Legacy Perfluoroalkyl Substances in Breastfed Chinese Infants: Renal Clearance, Body Burden, and Implications.

BACKGROUND: Human breast milk is a primary route of exposure to perfluoroalkyl substances (PFAS) in infants. To understand the associated risks, the occurrence of PFAS in human milk and the toxicokinetics of PFAS in infants need to be addressed. OBJECTIVES: We determined levels of emerging and legacy PFAS in human milk and urine samples from Chinese breastfed infants, estimated renal clearance, and predicted infant serum PFAS levels. METHODS: In total, human milk samples were collected from 1,151 lactating mothers in 21 cities in China. In addition, 80 paired infant cord blood and urine samples were obtained from two cities. Nine emerging PFAS and 13 legacy PFAS were analyzed in the samples using ultra high-performance liquid chromatography tandem mass spectrometry. Renal clearance rates (CLrenals) of PFAS were estimated in the paired samples. PFAS serum concentrations in infants (<1 year of age) were predicted using a first-order pharmacokinetic model. RESULTS: All nine emerging PFAS were detected in human milk, with the detection rates of 6:2 Cl-PFESA, PFMOAA, and PFO5DoDA all exceeding 70%. The level of 6:2 Cl-PFESA in human milk (median concentration=13.6 ng/L) ranked third after PFOA (336 ng/L) and PFOS (49.7 ng/L). The estimated daily intake (EDI) values of PFOA and PFOS exceeded the reference dose (RfD) of 20 ng/kg BW per day recommended by the U.S. Environmental Protection Agency in 78% and 17% of breastfed infant samples, respectively. 6:2 Cl-PFESA had the lowest infant CLrenal (0.009mL/kg BW per day), corresponding to the longest estimated half-life of 49 y. The average half-lives of PFMOAA, PFO2HxA, and PFO3OA were 0.221, 0.075, and 0.304 y, respectively. The CLrenals of PFOA, PFNA, and PFDA were slower in infants than in adults. CONCLUSIONS: Our results demonstrate the widespread occurrence of emerging PFAS in human milk in China. The relatively high EDIs and half-lives of emerging PFAS suggest potential health risks of postnatal exposure in newborns. https://doi.org/10.1289/EHP11403.